Combination of Durvalumab and Tremelimumab as Maintenance Treatment in Patients With Non Squamous and Squamous (NSCLC)

NCT03319316 | Withdrawn Phase 2 DMC

• 2 other identifiers: EORTC-16432017-001827-39
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, 2-arm open-label, randomized comparative phase II study in each of two separate cohorts (non-squamous NSCLC and squamous NSCLC) according to histology.

Conditions

Squamous Non-small Cell Lung Cancer; Non-Squamous Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The time interval between the date of randomization and the date of disease progression or death, whichever comes first.

  4.3 years from FPI

Secondary Outcomes (6)

• Overall Survival (OS)

  5 years from FPI

• Objective response rate according to RECIST 1.1;

  5 years from FPI

• Progression-free survival -2

  5 years from FPI

• Time to failure of 2nd treatment

  5 years from FPI

• Safety

  5 years from FPI

Study Arms (4)

Cohort 1 - Non-squamous - Arm A

EXPERIMENTAL

Patients receive a maintenance treatment of durvalumab + tremelimumab

Drug: Durvalumab; Drug: Tremelimumab

Cohort 1 - Non-squamous - Arm B

NO INTERVENTION

Patients receive a maintenance treatment of pemetrexed

Cohort 2 - Squamous - Arm A

EXPERIMENTAL

Patients receive a maintenance treatment of durvalumab + tremelimumab

Drug: Durvalumab; Drug: Tremelimumab

Cohort 2 - Squamous - Arm B

NO INTERVENTION

Patients will have observation

Interventions

Durvalumab DRUG

Combination of durvalumab + tremelimumab treatment

Cohort 1 - Non-squamous - Arm A; Cohort 2 - Squamous - Arm A

Tremelimumab DRUG

Combination of durvalumab + tremelimumab treatment

Cohort 1 - Non-squamous - Arm A; Cohort 2 - Squamous - Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of NSCLC; for non-squamous NSCLC: no known sensitizing EGFR-mutation, no known EML4-ALK translocation. When a patient with non-squamous NSCLC has a KRAS mutation, further testing for EGFR and EML4-ALK is not necessary. For squamous NSCLC, EGFR and EML4-ALK testing is not necessary.
• Availability of adequate in quality and quantity archived tumor material for IHC PD-L1 testing; (Preferably 15 but 8 mandatory slides or block of tumor tissue will be collected);
• Stage IIIB or IIIC not eligible for radical treatment or stage IV according to TNM8 (Ref. 6);
• Brain metastases should be treated with local therapy (stereotactic radiotherapy or whole brain radiotherapy), and patients should be asymptomatic, without treatment with steroids for four weeks before enrollment. Before enrollment, new brain imaging (contrast-CT or gadolinium-MRI) is needed to demonstrate that there is no progression in the brain when the last brain imaging is more than four weeks earlier. Screening for brain metastases is not necessary in patients that were previously not diagnosed with brain metastases and that are without signs indicative of brain metastases.
• ≥ 18 years of age at time of study entry;
• WHO performance status 0 or 1; at enrollment
• Body weight \> 30 kg at enrollment
• Evaluable disease with CT or MRI according to RECIST 1.1 (except for patients with a CR after 4 cycles of platinum-based doublet chemotherapy, these patients are also eligible);
• Stable disease or response by RECIST criteria response after 4 cycles of platinum-based doublet chemotherapy;
• Adequate normal organ and marrow function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology)AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal; for patients with liver metastases ≤ 5 x institutional upper limit of normal
• Measured or calculated creatinine clearance ≥45 mL/min by the Cockcroft-Gault formula (Appendix E)
• Haemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant or large cell neuro-endocrine variant
• Patients with known history of leptomeningeal carcinomatosis
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the study investigator
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study investigator
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, a CTLA-4 including tremelimumab or other checkpoint inhibitors or other immune therapy during the last 12 months
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, or steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable when it is not within 7 days of the first dose of study drug.
• Major surgical procedure (as defined by the study investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
• History of allogenic organ transplantation
• Receipt of live attenuated vaccination within 30 days prior to enrollement
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]).
• History of hypersensitivity to durvalumab, tremelimumab or any excipient
• Uncontrolled intercurrent illness including, but not limited to:
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

MeSH Terms

Interventions

durvalumab; tremelimumab

Study Officials

• Martin Reck, Pr

  Lungen Clinic Grosshansdorf, Grosshansdorf, Germany

  STUDY CHAIR

• Lizza Hendriks, MD

  Academisch Ziekenhuis Maastricht, The Netherlands

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 2-arm open-label randomized study in each of two separate cohorts (non-squamous and squamous NSCLC) according to histology.

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: October 24, 2017
• Study Start: November 1, 2018
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2022
• Last Updated: January 10, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share